Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036690 (sepsis)
 59,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Granulocyte colony-stimulating factor (G-CSF) increases the number of circulating granulocytes and decreases TNF production while improving survival in sepsis models. To study the effects of G-CSF administration on sepsis and rejection, 37 primary liver allograft recipients received intravenous recombinant human G-CSF (rhG-CSF; 5-10 micrograms/kg/day) for the first 7-10 days following transplantation, targeting a blood absolute granulocyte count of between 10,000 and 20,000 cells/mm3. These recipients were monitored prospectively for sepsis and rejection, as were the previous 49 primary liver allograft recipients who did not receive G-CSF. Both groups utilized identical protocol immunosuppression and standardized diagnosis and treatment of sepsis and rejection. Univariate and logistic regression analysis of risk factors for sepsis and rejection revealed no difference between the two patient groups. G-CSF-treated patients developed an increased absolute granulocyte count over time (P < 0.0001, repeated-measures analysis of variance). G-CSF-treated patients had a decreased number of sepsis episodes per patient (0.92 +/- 1.5 vs. 2.18 +/- 2.8, P < 0.02, t test), and a lower percentage of sepsis-related deaths (8% vs. 22%, P < 0.04, chi-square test). The incidence of acute rejection was decreased in the G-CSF-treated group (22% vs. 51%, P < 0.01, chi-square test). These pilot data support further investigation into G-CSF's favorable effects on sepsis and rejection.
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PMID:The use of granulocyte colony-stimulating factor after liver transplantation. 753 58

With the aim of increasing the dose intensity of chemotherapy in breast cancer, 14 patients with stage II-IV breast cancer were treated with FEC chemotherapy at 2 week intervals together with granulocyte colony-stimulating factor (G-CSF) 5 micrograms kg-1 s.c. on days 2-14. Five of six patients completed six courses of 5-fluorouracil 600 mg m-2, epirubicin 60 mg m-2 and cylcophosphamide 600 mg m-2 within 11 weeks. Eight patients were treated with 5-fluorouracil 700 mg m-2, epirubicin 70 mg m-2 and cyclophosphamide 700 mg m-2 and four had dose-limiting toxicity with sepsis, thrombocytopenia or mucositis. All patients who received G-CSF had satisfactory neutrophil counts by day 15 of each course. Cumulative anaemia and thrombocytopenia were observed, but treatment at the first dose was tolerable. Seven of eight patients with measurable disease had partial responses. This regimen permits a 50% increase in dose intensity compared with conventional treatment at 3 week intervals and warrants further evaluation.
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PMID:Phase I study of accelerated FEC with granulocyte colony-stimulating factor (Lenograstim) support. 754 38

We report a case of sepsis due to Clostridium septicum successfully treated with granulocyte colony-stimulating factor (GCSF). This case prompted our review of clostridial sepsis and considerations regarding the use of GCSF in cases of drug-induced neutropenia.
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PMID:Myonecrosis due to Clostridium septicum in a patient with unexplained neutropenia: successful treatment with granulocyte colony-stimulating factor. 754 Nov 62

Sepsis is a common cause of morbidity and mortality. Neutrophils are the major defense against bacterial invasion, and granulocyte colony-stimulating factor (G-CSF) augments both neutrophil number and function. In our study, 160 rabbits were inoculated transtracheally with 0.5 mL of a solution containing 10(4) colony forming units per milliliter of Pasteurella multocida. Twenty-four hours later, chest x-rays and quantitative blood cultures demonstrated pneumonia and bacteremia. Therapy was then begun with penicillin G and either recombinant human G-CSF (rG-CSF; 5 to 8 micrograms/kg subcutaneously) or placebo every day for 5 days. Arterial blood gases and 23 other parameters of organ function were performed before inoculation and serially thereafter. All rabbits underwent histologic examination of organs at the time of septic death or when sacrificed on day 6. A total of 149 rabbits survived long enough to initiate therapy. A significant increase in leukocytes by day 4 was found in the rG-CSF-treated group. There was a trend towards improved survival in the rG-CSF group (77% v 67%; P = .13, n = 149). Analysis of pretreatment variables revealed sepsis-induced leukopenia (< or = 2,800/microL) as the only predictor of significantly improved survival with rG-CSF treatment (57% v 39%; P = .04, n = 73). The majority of the survival benefit occurred within the first 24 hours of treatment. This was before the time that a significant difference in mean white blood cell (WBC) count was observed between the study groups, making intravascular leukocytosis an unlikely explanation for the survival advantage in the rG-CSF group. No significant difference in laboratory variables reflecting organ function was demonstrated between the groups. Histologic grading of inflammation (0, normal, to 6, necrosis) in seven organs revealed that the surviving rabbits had mild but statistically significant increased inflammation in the liver, spleen, and noninoculated lung in the rG-CSF versus placebo groups (liver: 2.6 v 1.5, P < or = .0001; spleen: 3.2 v 2.3, P < or = .0001; and noninoculated lung: 2.9 v 2.5, P = .04). Administration of rG-CSF, in addition to penicillin G, in immune competent rabbits with gram-negative sepsis complicated by leukopenia significantly improved survival over antibiotics alone. The administration of rG-CSF in early sepsis for a short therapeutic duration was not associated with any clinically evident toxicity. Clinical trials using rG-CSF in septic patients with leukopenia are indicated.
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PMID:Granulocyte colony-stimulating factor versus placebo in addition to penicillin G in a randomized blinded study of gram-negative pneumonia sepsis: analysis of survival and multisystem organ failure. 754 3

The therapeutic efficacy of granulocyte colony-stimulating factor (G-CSF) was studied in a model of fulminant sepsis in rats. Polymicrobial peritonitis was induced by a 4 mm cecal perforation and 10 micrograms/kg recombinant human G-CSF was given intravenously every 12 h, with the first dose at sepsis induction or 4 h post-induction. Rats were sacrificed at various intervals throughout sepsis to measure levels of neutrophil progenitors in the bone marrow and neutrophils and bacteria in blood and peritoneal fluid. Sepsis gave a sustained neutropenia and bacteremia, but did not affect numbers of blast- or GM-colonies, and only a delayed and moderate proliferation of G-clones was seen. Treatment with G-CSF at sepsis induction improved myelopoiesis by doubling the numbers of GM- and G-progenitors at 12 and 24 h post-induction. Concentrations of neutrophils increased twofold in blood and 5-fold in peritoneal fluid, while bacteria counts in the same compartments declined logarithmically. Mortality was 92% in untreated sepsis and declined to 46% when G-CSF therapy was started at sepsis induction, and to 42% following 4 h delayed therapy.
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PMID:Granulocyte colony-stimulating factor improves myelopoiesis and host defense in fulminant intra-abdominal sepsis in rats. 755 81

Immunotherapy can be defined as treatment directed at augmenting host immune defence mechanisms. Non-antimicrobial therapies and immunoprophylaxis in bone marrow transplantation (BMT) can be subdivided into three broad categories: passive immunotherapy with intravenous immunoglobulin (IVIG); cytokine therapy; and anti-endotoxin-directed treatments. Most studies using IVIG in BMT are prophylactic and suffer from variability in study design, type of IVIG and dosing regimens. Various effects on viral and bacterial infections and graft-versus-host disease (GVHD) have been reported but few if any have shown benefit in terms of improved patient survival. Moreover the immunomodulatory effect of immunoglobulin G preparations is frequently overlooked. With the exception of cytomegalovirus (CMV) pneumonitis, there is little evidence of benefit in the treatment of established infections and the relative benefits of hyperimmune preparations are poorly established. The development of haemopoietic growth factors has led to the widespread use of cytokines in BMT. The benefits of these agents both in the prevention of fever and infection and as adjuvants to standard antimicrobial therapy in established infection (e.g. invasive mycoses) are rapidly becoming apparent. Both human recombinant granulocyte-macrophage colony-stimulating factor (rhGM-CSF) and granulocyte colony-stimulating factor (rhG-CSF) have been shown to accelerate granulocyte recovery following BMT and reduce fever days, antibiotic usage and hospitalization. RhGM-CSF appears superior in these respects. The roles of interleukin 1 (IL1), IL3, IL6 and interferons are also under evaluation. As with the much publicised studies using anti-endotoxin antibodies as therapy in sepsis, there is little evidence of benefit in the few studies performed in BMT patients.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Immunotherapy and immunoprophylaxis in bone marrow transplantation. 756 Sep 54

Reproducible and characteristic clinical findings of fever, skin rash, capillary leak and pulmonary infiltrates have been observed during engraftment in patients with autologous bone marrow (BM) and/or peripheral stem cell transplantation (PSCT). Two hundred and forty-eight patients were analyzed retrospectively to establish the clinical entity, to characterize the clinical course, and to find clinical variables affecting the incidence of the syndrome. One hundred and eight cases (83.7 +/- 9.4%) of fevers occurring in the periengraftment period (PEN) not associated with positive cultures, biopsies, or clinical signs of infection did not reveal delayed documentation of concealed infection in 2 weeks after engraftment. Capillary leak, pulmonary infiltrates, hypoxia, non-infectious neutropenic fever of engraftment and skin rash were found to be interrelated (all P < 0.01 except for hypoxia vs rash; P < 0.05). By stepwise discriminant analysis, one hundred and thirty-two patients (58.9 +/- 6.4%) were shown to have both skin rash and non-infectious neutropenic fever, thereby constituting the syndrome. Sepsis in the first week of neutropenia decreased the incidence of the syndrome (58.5 +/- 7.7% with sepsis, 89.6 +/- 4.7% without sepsis, P < 0.01). Post-transplant granulocyte colony-stimulating factor increased the incidence of the syndrome (79 +/- 4.6% with G-CSF vs 48.3 +/- 8.2% without G-CSF, P < 0.01). In bone marrow transplantation (BMT), the median time of onset of the syndrome was 7 days (range 4-22 days) post-transplant with a median duration of 11 days (range 4-28 days) of the initial phase. Thirty-nine patients (17.4 +/- 5.0%) revealed a recurrent pattern during the 5th week post-transplant.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Engraftment syndrome in autologous bone marrow and peripheral stem cell transplantation. 758 Nov 19

Patients with malignant astrocytoma continue to respond poorly to chemotherapy and have a dismal prognosis. Cyclophosphamide (CTX) and etoposide demonstrate activity against malignant astrocytoma at standard dosages, with bone marrow suppression as the limiting toxicity. In order to allow dose intensification, minimize leukopenia, and improve efficacy granulocyte colony-stimulating factor (G-CSF) was used in combination with CTX and etoposide. The protocol consisted of CTX (2 mg/m2/d, days 1, 2), etoposide (200-300 mg/m2/d, days 1-3), and G-CSF (5-10 micrograms/d subcutaneously, days 4-18), every 4 weeks. Nine evaluable patients (7 glioblastoma multiforme, 2 anaplastic astrocytoma) were treated, ranging in age from 26-67 (mean 41). One of 9 patients responded (11%) with a partial response (13+ months), 3 had stable disease (33%; 8, 5, 2.5 months), and 5 had progressive disease (3, 2.5, 2, 1.5, 1 months). The median time to progression for responders was 6.5 months, while overall it was 2.5 months. Overall median survival was only 7.0 months. Toxicity was frequent and severe, typically delaying treatment cycles. The most common complications were severe myeolosuppression (9), sepsis (8), rash (6), urinary infection (5), and anorexia (5). Treatment delays caused by infections and other complications occurred often, abrogating the intended dose intensification. The received dose intensity (DI) for CTX was 400-425 mg/m2/week (relative DI 0.41), while for etoposide it was 75 mg/m2/week (relative DI 0.42). In summary, as used in this protocol, dose intensive chemotherapy with CTX, etoposide, and G-CSF does not improve efficacy over standard regimens and results in excessive toxicity.
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PMID:Attempted dose intensified cyclophosphamide, etoposide, and granulocyte colony-stimulating factor for treatment of malignant astrocytoma. 759 59

Granulocyte colony-stimulating factor (G-CSF) stimulates the production and function of neutrophils (PMNs). Administration of G-CSF to non-neutropenic animals has been shown to improve survival in experimental models of infection, but PMNs have been implicated as mediators of acute lung injury induced by lipopolysaccharide (LPS) or bacteremia. Thus G-CSF-induced neutrophilia might be deleterious in sepsis. To investigate this possibility, we studied four groups of pigs: G+E50 (n = 6) were pretreated for 5 days with recombinant bovine (rb) G-CSF (5 micrograms/kg/day) and then challenged with LPS (50 micrograms/kg); NS+E50 (n = 6) were similarly pretreated with saline and challenged with LPS (50 micrograms/kg); E250 (n = 6) were not pretreated and were infused with a larger dose of LPS (250 micrograms/kg); RL (n = 7) were controls infused with lactated Ringer's solution. Pretreatment with rbG-CSF increased the peripheral absolute neutrophil count approximately fivefold (p < 0.05 vs. RL group). Comparisons of the NS+E50 and G+E50 groups showed that pretreatment with rhG-CSF did not affect LPS-induced alterations in mean arterial blood pressure or arterial oxygenation. Indices of pulmonary injury also were similar in these two groups, although pulmonary edema and protein leakage into alveoli were greater in the E250 group. We conclude that G-CSF-induced neutrophilia does not adversely effect physiologic responses to LPS in pigs.
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PMID:Effect of granulocyte colony-stimulating factor on systemic and pulmonary responses to endotoxin in pigs. 768 31

Our purpose was to evaluate the ability of recombinant human granulocyte colony-stimulating factor (r-metHuG-CSF) as an adjunct to induction chemotherapy of acute lymphoblastic leukemia (ALL) to ameliorate chemotherapy-induced neutropenia and thus allow patients to receive full doses of chemotherapy on time. Sixteen consecutive patients with adult ALL (13 de novo, three relapsed) were treated with induction chemotherapy according to the BMFT protocol and received in addition r-metHuG-CSF (200 micrograms/m2/day). Patients who were treated with the same induction chemotherapy but without G-CSF between 1982 and 1990 served as controls. Fifteen of the 16 patients achieved complete hematological remission. One patient died because of fungal septicemia. Compared with historical controls, G-CSF-treated patients had a significantly faster neutrophil recovery in phase I, resulting in neutrophil counts > 1000/microliters at day 17 vs day 26 (in median) in controls. In phase II, the onset of severe leukocytopenia (< 1500/microliters) was significantly (p = 0.01) delayed and the degree of leukocytopenia less pronounced (mean nadir 3300/microliters) in G-CSF-treated patients compared with controls (1880/microliters). The number of days of febrile neutropenia was not different in phase I. In phase II it was lower in study patients (0 vs 1.1 days), but the difference did not reach statistical significance (p = 0.09). Full doses of chemotherapy could be given on time to 11/13 (85%) G-CSF patients but to only 7/30 (23%) controls. These data indicate that (a) G-CSF can be given along with chemotherapy in induction treatment of ALL without compromising efficacy; (b) the duration of neutropenia in phase I is markedly shortened and the degree of leukocytopenia in phase II ameliorated; (c) these beneficial effects allow patients to receive full doses of chemotherapy on time.
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PMID:Granulocyte colony-stimulating factor (G-CSF) as an adjunct to induction chemotherapy of adult acute lymphoblastic leukemia (ALL). 768 4


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